| 引用本文: |
许娟, 邹小云, 贾守宁, 祁永福, 李海霖, 李军茹.胃糜舒调控IL-6/STAT3/RORγt Th17分化信号通路治疗幽门螺杆菌感染胃炎小鼠的机制研究[J].湖南中医药大学学报,2026,46(7):1312-1322[点击复制] |
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| 胃糜舒调控IL-6/STAT3/RORγt Th17分化信号通路治疗幽门螺杆菌感染胃炎小鼠的机制研究 |
| 许娟,邹小云,贾守宁,祁永福,李海霖,李军茹 |
| (青海大学医学院, 青海 西宁 810016;青海省中医院, 青海 西宁 810001) |
| 摘要: |
| 目的 研究胃糜舒治疗幽门螺杆菌感染胃炎小鼠的效果及作用机制。方法 36只小鼠随机分为对照组、模型组、胃糜舒低剂量组[7.43 g/（kg·d）]、胃糜舒中剂量组[14.85 g/（kg·d）]、胃糜舒高剂量组[29.70 g/（kg·d）]、阳性药物组[丽珠维三联3.20 g/（kg·d）]，每组6只。除对照组外，其余5组小鼠各给予抗生素混合溶液（庆大霉素1.2 mg/mL、氨苄西林10 mg/mL、阿奇霉素10 mg/mL） 0.3 mL，灌胃3 d，禁食1 d后开始幽门螺杆菌菌液灌服。检测胃糜舒对幽门螺杆菌感染胃炎小鼠的治疗情况，通过HE染色、PAS染色、瑞氏-吉姆萨染色观察胃组织损伤，采用ELISA检测白细胞介素（IL）-6、肿瘤坏死因子-α（TNF-α）、IL-17水平；采用流式细胞术检测辅助性T细胞17（Th17）细胞比例；免疫组织化学检测中性粒细胞标志物淋巴细胞抗原6复合物基因座G（Ly6G），免疫荧光共染髓过氧化物酶（MPO）、瓜氨酸化组蛋白H3（CitH3）；通过Western blot检测IL-6、信号转导与转录激活因子3（STAT3）、磷酸化STAT3（p-STAT3）、维甲酸相关孤儿受体γt（RORγt）蛋白表达水平。结果 与对照组比较，模型组胃组织损伤严重，黏膜层大片变性坏死，伴有炎症细胞浸润，黏液增多；与模型组相比，胃糜舒低、高剂量组损伤减轻，黏膜层局部变性坏死，炎症细胞浸润较多，胃糜舒低剂量组黏液变化轻微，高剂量组黏液减少；胃糜舒中剂量组损伤减轻，黏膜层轻微变性坏死，炎症细胞浸润减少，黏液减少。与对照组相比，模型组IL-6、TNF-α、IL-17水平增加（P<0.01）；与模型组相比，胃糜舒低、中、高剂量组IL-6、TNF-α、IL-17水平降低（P<0.05和P<0.01）。与对照组相比，模型组Th17细胞比例增加（P<0.01）；与模型组相比，胃糜舒低、高剂量组Th17细胞比例差异无统计学意义，胃糜舒中剂量组Th17细胞比例降低（P<0.05）。与对照组相比，模型组Ly6G、MPO、CitH3阳性表达量增加（P<0.01）；与模型组相比，胃糜舒低、中、高剂量组Ly6G、MPO、CitH3阳性表达量降低（P<0.01）。与对照组相比，模型组IL-6、p-STAT3、RORγt蛋白表达水平增加（P<0.01），STAT3蛋白表达差异无统计学意义（P>0.05）；与模型组相比，胃糜舒低、中、高剂量组IL-6、p-STAT3、RORγt蛋白表达降低（P<0.05和P<0.01），STAT3蛋白表达差异无统计学意义（P>0.05）。结论 胃糜舒可能通过调控IL-6/STAT3/RORγt Th17分化信号通路，减轻幽门螺杆菌感染胃炎小鼠的胃组织损伤、调节Th17细胞极化和中性粒细胞诱捕网形成等发挥治疗作用，为慢性糜烂性胃炎治疗提供新参考。 |
| 关键词: 幽门螺杆菌感染胃炎|胃糜舒|IL-6/STAT3/RORγt信号通路|Th17细胞分化|中性粒细胞诱捕网 |
| DOI：10.3969/j.issn.1674-070X.2026.07.002 |
| 投稿时间：2025-10-18 |
| 基金项目:2023年中央财政转移支付地方项目——中药创新能力提升项目（国中医药科技中药便函〔2023〕24号）。 |
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| Mechanism underlying the therapeutic effects of Weimishu on Helicobacter pylori-induced gastritis in mice via regulation of the IL-6/STAT3/RORγt-mediated Th17 differentiation signaling pathway |
| XU Juan, ZOU Xiaoyun, JIA Shouning, QI Yongfu, LI Hailin, LI Junru |
| (Qinghai University Medical College, Xining, Qinghai 810016, China;Qinghai Provincial Hospital of Traditional Chinese Medicine, Xining, Qinghai 810001, China) |
| Abstract: |
| Objective To investigate the therapeutic effects and mechanism of action of Weimishu in treating Helicobacter pylori(Hp)-induced gastritis in mice. Methods A total of 36 mice were randomly divided into control, model, low- [7.43 g/(kg·d)], medium- [14.85 g/(kg·d)], and high-dose Weimishu [29.70 g/(kg·d)], and positive drug groups (Lizhuwei Sanlian 3.20 g/(kg·d)), with six mice in each group. Except for the control group, mice in the other 5 groups were administered 0.3 mL of a mixed antibiotic solution (gentamicin 1.2 mg/mL, ampicillin 10 mg/mL, azithromycin 10 mg/mL) by gavage for three consecutive days and then were fasted for 1 day before oral gavage with Hp suspension. The therapeutic effects of Weimishu on Helicobacter pylori-induced gastritis in mice were evaluated by the following methods: HE staining, PAS staining, and Wright-Giemsa staining were used to observe the gastric tissue injury; ELISA was used to determine the levels of IL-6, TNF-α, and IL-17; Flow cytometry was employed to analyze the proportion of T helper 17 (Th17) cells; immunohistochemistry was performed to check the neutrophil marker lymphocyte antigen 6 complex locus G (Ly6G), while immunofluorescence co-staining was used to assess myeloperoxidase (MPO) and citrullinated histone H3 (CitH3). The protein expression levels of IL-6, signal transducer and activator of transcription 3 (STAT3), phosphorylated STAT3 (p-STAT3), and retinoic acid-related orphan receptor γt (RORγt) were tested by Western blot. Results Compared with the control group, the model group exhibited severe gastric tissue injury characterized by extensive mucosal layer degeneration and necrosis, inflammatory cell infiltration and increased mucus secretion. Compared with the model group, gastric injury was alleviated in the low- and high-dose Weimishu groups, with focal mucosal degeneration and necrosis, and marked inflammatory cell infiltration, slight changes in mucus secretion in the low-dose Weimishu group, decreased mucus secretion in the high-dose group. The medium-dose Weimishu group showed alleviated injury, mild mucosal layer degeneration and necrosis, reduced inflammatory cell infiltration, and reduced mucus secretion. Compared with the control group, the levels of IL-6, TNF-α and IL-17 in the model group increased (P<0.01). Compared with the model group, the low-, medium- and high-dose Weimishu groups showed decreased levels of IL-6, TNF-α and IL-17 (P<0.05 and P<0.01). Compared with the control group, the proportion of Th17 cells in the model group increased (P<0.01). Compared with the model group, there was no significant difference in the proportion of Th17 cells in the low- and high-dose Weimishu groups, while the medium-dose group showed a decreased proportion of Th17 cells (P<0.05). Compared with the control group, the Ly6G-positive staining area, and the positive cell rates of MPO and CitH3 increased in the model group (P<0.01). Compared with the model group, the Ly6G-positive staining area, and the positive cell rates of MPO and CitH3 decreased in low-, medium- and high-dose Weimishu groups (P<0.01). Compared with the control group, the protein expression levels of IL-6, p-STAT3 and RORγt in the model group increased (P<0.01), and no significant difference was observed in the expression of STAT3 protein. Compared with the model group, the protein expression levels of IL-6, p-STAT3 and RORγt in the low-, medium- and high-dose Weimishu groups decreased (P<0.05 and P<0.01), and the expression of STAT3 protein was not statistically significant. Conclusion Weimishu may exert therapeutic effects by regulating the IL-6/STAT3/RORγt signaling pathway involved in Th17 cell differentiation, thereby alleviating gastric tissue injury, modulating Th17 cell polarization, and inhibiting neutrophil extracellular trap formation in mice with Hp-induced gastritis. These findings may provide a new therapeutic perspective for the treatment of chronic erosive gastritis. |
| Key words: Helicobacter pylori-induced gastritis|Weimishu|IL-6/STAT3/RORγt signaling pathway|Th 17 cell differentiation|neutrophil extracellular traps |
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